Views:5 Author:Golden Horizon (Chengdu) Technology Co., Ltd. Publish Time: 2017-03-09 Origin:Golden Horizon (Chengdu) Technology Co., Ltd.
Sometimes it seems nature has a “one-up” on humans. That’s certainly the case with some plant extracts that have been shown in the past to prolong life in animal models, and others that have lent compounds to our search for more sophisticated pharmaceuticals.
Now, geneticists have turned their attention to terpenoids (or isoprenoids), the largest class of natural products that includes more than 30,000 individual compounds.
Since it’s substantially easier to develop a new drug based on a compound that has already been approved, researchers from the Engelhardt Institute of Molecular Biology and Moscow Institute of Physics and Technology (Russia) delved into the unexplored benefits of Abisil, a drug based on Siberian fir terpenoids that is already used as an anti-inflammatory and antibacterial.
In past studies, terpenoids have exhibited potential anti-aging and anti-cancer properties. For example, extracts from Rosa damascene, which is rich in the terpenoid citronellol, have been shown to increase the lifespan ofDrosophila by protecting against iron toxicity and enhancing resistance to oxidative stress. Betulinic acid, a lupane-type triterpene derived from the birch tree, has demonstrated antibacterial, antimalarial and anti-inflammatory properties, activity against HIV and cytotoxicity toward cancer cells.
To study the effect of Siberian fir terpenoids on cellular aging, the researchers used a technique called cell passaging on human connective tissue cells, known as fibroblasts. Passaging, or subculturing, refers to the process of transferring an existing cell culture to a fresh growth medium. Passaging is necessary due to the accumulation of toxic products of cell metabolism and the depletion of nutrients. The number of passages a culture has experienced gives an idea of how many divisions the cells have undergone and therefore how much they have aged—providing scientists with an accurate model for aging.
Additionally, the researchers used variations in the amount of RNA produced by a cell as aging markers. These variations in gene activity were compared between cells from different passages—those untreated and those exposed to the fir substance.
According to the researchers, 21 genes in the fibroblasts from the 6th passage exhibited increased expression (more RNA was produced by the cells), with 16 genes from the same passage decreasing. That’s compared to the 43 genes from the 13th passage that increased, and the 67 that decreased.
“This means that as a cell ages, the effect of Siberian fir terpenoids on gene expression becomes more pronounced,” the researchers explained.
“Exposure of cells to the test compound caused an increase in the expression of the two genes GADD45B and GADD45A by factors of 2 and 1.5 respectively. Both of them belong to a gene family whose members have been linked to tumor suppression and longevity. In addition, these genes are known to mediate the effects of several chemotherapeutic drugs,” the researchers continued.
Other genes that showed overexpression upon exposure of cancer cells to the fir test compound include DUSP1–2, DUSP4–6 and DUSP8. Genes of the DUSP family are responsible for the suppression of the MAPK signal transduction cascade, which means they act as tumor suppressors and chemotherapy mediators.
Overall, the research team found that treatment with Siberian fir terpenoids coincided with an increase in the expression of heat shock genes by a factor of 1.5 to 3. These genes play a major role in the assembly, folding and transport of complex proteins, as well as in degrading and recycling unneeded proteins.
Thus, the scientists concluded the Abisil drug is capable of restoring gene expression in senescent cells to the level of younger cells, and believe it has potential anti-aging and anti-cancer properties that need to be explored further in the future.
Their paper was recently published in the biomedical journal Oncotarget.